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Molecular motors: new designs and applicationsRoke, Gerrit Dirk

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Chapter 1

Molecular rotary motors:

Unidirectional motion around

double bonds

The field of synthetic molecular machines has quickly evolved in recent years, growing

from a fundamental curiosity to a highly active field of chemistry. Many different

applications are being explored in areas such as catalysis, self-assembled and

nanostructured responsive materials, and molecular electronics. Rotary molecular motors

hold great promise for achieving dynamic control of molecular functions as well as for

powering nanoscale devices. However, for these motors to reach their full potential, still

many challenges need to be addressed. In this perspective, we focus on the design

principles of rotary motors featuring a double bond axle and discuss the major challenges

that are ahead of us. Although great progress has been made, further design

improvements, for example in terms of efficiency, energy input and environmental

adaptability, will be crucial in order to fully exploit the opportunities that these rotary

motors offer.

This chapter was published as: D. Roke, S. J. Wezenberg, B. L. Feringa, Proc. Natl. Acad. Sci.

U.S.A. 2018, 115, 9423 – 9431.

10

Chapter 1

1.1 Introduction

Control of motion at the molecular scale has intrigued chemists for a very long time. The

quest for overcoming random thermal (Brownian) motion has culminated in the

emergence of synthetic molecular machines,[1–7]

including motors,[8–12]

muscles,[13]

shuttles,[14]

elevators,[15]

walkers,[16]

pumps[17–19]

and assemblers.[20]

By taking inspiration

from the fascinating dynamic and motor functions observed in biological systems (e.g.

ATPase and bacterial flagella),[21]

the field of synthetic molecular machines has evolved

rapidly in recent years. This is due to major advances in supramolecular chemistry and

nanoscience, the emergence of the mechanical bond[7]

and the development of dynamic

molecular systems.[22]

A variety of potential applications is now being considered in areas

ranging from catalysis[23]

and self-assembly[24]

to molecular electronics[25,26]

and responsive

materials.[27,28]

Furthermore, translation of motion from the molecular scale to the

macroscopic scale allows for dynamically changing material properties and the movement

of larger objects. Cooperativity and amplification across several length scales can be

achieved, for example, by incorporating molecular machines in gels,[29,30]

liquid

crystals,[27,31]

polymers[32]

or by anchoring them to surfaces,[33,34]

allowing the control of a

variety of properties including surface wettability,[33,34]

contraction or expansion of gels[29]

and actuation of nanofibers in response to their environment.[35]

This leap from static to

dynamic materials clearly demonstrates the potential of molecular machines. Although

much effort has already been devoted to the development of molecular motors and

machines as well as the elucidation of their operational mode, a great deal of design

improvements are needed in order to fully exploit the potential in practical applications.

Ideally, molecular motors can operate with high efficiency, durable energy input (fuel),

can be easily adapted to a specific environment or application, are compatible with

specific functions and can be synchronized and act in a cooperative manner.

Where the pioneering work of Sauvage, Stoddart, and others successfully led to stimuli-

controlled translational and rotary motion in mechanically interlocked systems,[1,36–39]

the

induction of unidirectional rotary motion posed a major challenge. Distinct approaches,

including those based on catenanes,[39]

surface confined systems,[40]

and aryl-aryl single

bond rotation,[8,41,42]

have been taken over the last two decades to develop molecular

motors capable of such unidirectional rotation when supplied by energy in the form of

light, chemical stimuli, or electrons.[11]

In this perspective, we focus on rotary motors that

contain a double bond axle (Figure 1.1). Although it may seem unusual to use a double

bond as rotary axle since the rotation is restricted, stimuli such as light can induce rotation

(cf. isomerization) as is most elegantly seen in the process of vision.[43]

As such,

autonomous and repetitive unidirectional rotation has been successfully achieved in

multiple systems, all of them are driven by light. Here, we discuss the key design principles

of these systems and furthermore, a perspective on key challenges and possible future

developments is provided.

11

Molecular rotary motors: Unidirectional motion around double bonds

Figure 1.1. Schematic representation of unidirectional rotary motion around a double bond

axle.

1.2 Motors based on overcrowded alkenes

At the very basis of overcrowded alkene-based molecular motors is a photochemical cis-

trans isomerization around their central carbon-carbon double bond. For stilbene, this

process has been studied already for more than half a century.[44]

Due to the symmetry of

stilbene, there is no directional preference in the isomerization process. It was shown in

1977 that the introduction of steric bulk around the double bond distorts the otherwise

planar geometry giving rise to helical chirality.[45]

This feature was further exploited to

develop a chiroptical switch, in which two pseudoenantiomeric forms with opposing

helical chirality could be selectively addressed.[46]

This work formed the basis for the

design and synthesis of the first molecule capable to undergo unidirectional 360° rotation

around a double bond, which our group reported in 1999.[9]

It is based on an overcrowded

alkene, with two identical halves on each side of the double bond (the rotary axle) ((P,P)-

trans-1 in Scheme 1.1a). Due to steric interactions between the two halves, in what is

referred to as the fjord region, the molecule is twisted out of plane resulting in a helical

shape. The first molecular motor featured two stereogenic methyl substituents which are

preferentially in a pseudo-axial orientation due to steric crowding. These stereocenters

dictate the helical chirality in both halves of the molecule and hence, the direction of

rotation. A full rotary cycle consists of four distinct steps: Two photochemical and

energetically uphill steps and two thermally activated and energetically downhill steps.

Starting from (P,P)-trans-1 (Scheme 1.1a), irradiation with UV-light (280 nm) induces a

trans to cis isomerization around the double bond leading to isomer (M,M)-cis-1 with

opposite helical chirality. This photoisomerization is reversible and under continuous

irradiation a photostationary state (PSS) is observed in which for this particular case the

ratio of cis to trans is 95:5. In (M,M)-cis-1 the methyl substituents end up in an

energetically less favorable pseudo-equatorial orientation. To release the build-up strain,

a thermally activated process occurs, in which both halves slide alongside each other

inverting the helicity from left- (M,M) to right-handed (P,P) and allowing the methyl

12

Chapter 1

substituents to readopt the energetically favored pseudo-axial orientation. The

photogenerated states, which are prone to such a thermal helix inversion (THI) process,

have often been referred to as ‘unstable’ or ‘metastable’ states. The THI is energetically

downhill and effectively withdraws the higher-energy isomer such as (M,M)-cis-1 from the

photoequilibrium mixture and hence, completes the unidirectional 180° rotary motion.

The second part of the cycle proceeds in a similar fashion as a second photoisomerization

step affords (M,M)-trans-1 (PSS trans to cis ratio of 90:10) with the methyl substituents

again in the pseudo-equatorial position. A second THI then reforms (P,P)-trans-1 and a full

360° rotation cycle is completed.

The so called second generation light-driven molecular rotary motors, consisting of

distinct upper (rotor) and lower (stator) halves and bearing only a single stereogenic

center (Scheme 1.1c), was presented shortly after.[47]

Analogous to the first generation

motors, 360° rotary motion can be achieved by a sequence of a photochemical and

thermal steps. The design, with non-identical halves, allowed for a much broader scope of

functionalization, in particular for surface anchoring through the stator, and paved the

way for many different applications,[12]

as shown in Figure 1.2.

The development of second generation motors revealed that the presence of only one

stereogenic center is sufficient to induce unidirectional rotation. This raised the question if

unidirectional rotation can be achieved in the absence of any stereocenters.[48]

To address

this question, symmetrical motors were synthesized bearing two rotor units. These third

generation motors only have a pseudo-asymmetric center and still unidirectional rotary

motion around both axles was found to occur.

Since our first reports on molecular rotary motors based on overcrowded alkene, great

effort has been dedicated to the understanding of their functioning, especially the key

parameters that govern the isomerization processes, and the use of new insights to adapt

the structural design.[11]

This has resulted in a large collection of overcrowded alkene-

based motors with different properties, which have been applied successfully to induce

motion at the molecular scale as well as the nanoscale and macroscale.[27,34,49]

The main

aspects that have been investigated and will be discussed in the next sections are the

speed of rotation, the excitation wavelength and the efficiency of the motors.

13

Molecular rotary motors: Unidirectional motion around double bonds

Scheme 1.1. (a) Rotary cycle of a first generation motor based on overcrowded alkene (b)

Top view of the rotary cycle (c) Structures of second and third generation molecular

motors.

14

Chapter 1

Figure 1.2: Molecular motors based on overcrowded alkene in different types of

applications.

1.2.1 Rotational speed adjustment

For every different application of molecular motors, for example in soft materials or

biological systems, often a distinct frequency of rotation is desired. The photochemical

steps proceed on a timescale of picoseconds, making the usually much slower THI the rate

limiting step.[50]

Considerable research effort in our group has been devoted to fully

understand the THI and to altering the rotational speed by structural modifications.

Throughout the years, DFT calculations have proven to be useful in predicting thermal

barriers prior to the synthesis of new motors and in interpreting experimental results.[51,52]

Although many factors may influence the rate of the THI, steric interactions within the

molecule play a dominant role. Generally, two approaches have been taken to speed up

the THI (Figure 1.3): (i) By lowering the thermal barrier through a decrease in the steric

hindrance in the fjord region, or (ii) by raising the energy of the unstable state relative to

the transition state. Additionally, electronic effects on the barrier of the THI were studied

by introducing a strong push-pull system over the central double bond in a second

generation motor.[53]

A decrease in the barrier of the THI as well as for the thermal E-Z

isomerization was observed. Consequently, upon generation of the unstable state, both a

‘forward’ THI and a competing ‘backward’ thermal E-Z isomerization took place in this

push-pull system, reducing the efficiency of the resulting motor.

15

Molecular rotary motors: Unidirectional motion around double bonds

Figure 1.3. Approaches for speeding up the THI either through i) a decrease in steric

hindrance in the fjord region or ii) by destabilization of the unstable state with respect to

the transition state.

For first generation motors, the THI for unstable cis and trans isomers are different

processes and therefore have different rates.[9]

Modifications to the design of the

molecular motor can have complex and sometimes opposite effects on these rates. For

example, the introduction of more steric bulk at the stereogenic center, by replacing the

methyl substituent in motor 4 with an isopropyl group, accelerates the rate of thermal

isomerization from the unstable to the stable cis form, but decreases the rate going from

the unstable to the stable trans isomer (Figure 1.4).[54]

The latter process was found to be

so slow that an intermediate state could be observed with mixed helicity, that is (P,M)-

trans-5, suggesting that the THI is a stepwise process. This kind of behavior was already

predicted for related overcrowded alkenes that do not have stereogenic methyl

substituents, which according to calculations racemize between (M,M) and (P,P)-helical

structures via an intermediate structure with (P,M)-helicity.[55]

This example, however,

16

Chapter 1

remains so far the only case in which such a stepwise mechanism for the THI in first

generation motors is observed. To decrease the amount of steric hindrance in the fjord

region and hence lower the energy barrier for THI, the central six-membered ring was

changed to a five-membered ring (Motor 6 in Figure 1.4).[56]

It has to be noted that upon

reducing the ring size from six- to five-membered, conformational flexibility is lost. As a

consequence, the unstable states are most likely further destabilized as the steric

hindrance cannot be relieved by folding, which additionally contributes to increased rates

for the THI.

Figure 1.4. Structural variations of first generation molecular motors and effects on t1/2 of

THI process.

In an attempt to further destabilize the unstable states, overcrowded alkene 7 was

synthesized, which has two tert-butyl instead of methyl substituents at the stereogenic

center.[57]

However, these substituents cause too much steric hindrance impeding the

unidirectional motion. Another approach is to replace the naphthalene moieties with

xylene moieties (motor 8).[58]

In this design, the xylyl methyl substituents cause the

necessary steric hindrance in the fjord region. X-ray analysis shows that these methyl

substituents are more sterically demanding in the trans-isomer, forcing the molecule in a

more strained conformation, also leading to destabilization of the unstable trans isomer.

The barrier of the THI from unstable trans to stable trans was found to be lower in motor

8 with respect to motor 6. On the other hand, the increased steric hindrance in the fjord

region causes a higher barrier for the unstable cis to stable cis isomerization, reflecting the

complex and opposite effect that (often subtle) changes in the molecular design may have

on the rates of these two THI processes.

Similar systematic structural modifications have been made to second generation motors

to alter their speed of rotation. Initial studies mainly involved motors of the general

structure 9 (Figure 1.5) in which the bridging atoms (X and Y) where varied.[47,51,52]

Half-

lives of the unstable states ranging from 233 h (X = S, Y = C(CH3)) to 0.67 h (X = CH2, Y = S)

were measured. The conformationally flexible six-membered rings allow for the molecule

to release some of the strain around the double bond that is build up in the

17

Molecular rotary motors: Unidirectional motion around double bonds

photoisomerization step. DFT calculations have shown that, in case of a six-membered

ring, the THI is a stepwise process and multiple transition states have been identified.[51,52]

Also here the change to a five membered ring in the stator makes the molecule more rigid.

Again, this results in an increased barrier for the THI in compound 10, up to the point

where a thermal E-Z isomerization becomes favored over the THI and a bistable switch is

obtained.[59]

When only in the upper half rotor a five-membered ring is introduced (motor

11), the rotational speed dramatically increases up to the MHz regime.[60]

Motor 12,

bearing two five membered rings, on the other hand, has a lower barrier in analogy to the

first generation motors due to a decrease in the steric hindrance in the fjord region.[61]

The

steric hindrance, and as a consequence the THI barrier, was further reduced by replacing

the naphthalene moiety in the upper half with xylene or benzothiophene (motor 13).[58,62]

Furthermore, larger substituents have been placed at the stereogenic center to increase

the rate of the THI[63,64]

and DFT calculations showed that this decrease is due to

destabilization of the unstable state, effectively lowering the barrier for THI.

Figure 1.5. Structural variations of second generation molecular motors.

The speed of the rotary motors is also dependent on the solvent.[65,66]

In a systematic

study of motors with pending arms of varying flexibility and length it was established that

solvent polarity plays a minor role, but that in particular enhanced solvent viscosity for

motor systems with rigid arms decreases THI drastically.[67]

The results were analyzed in

terms of a free volume model and it is evident that matrix effects (solution, surface,

polymer, liquid crystal) comprise a challenging multiparameter aspect in applying

molecular motors. In all these examples, changing the speed of rotation of a molecular

motor requires a redesign of the molecule and multistep synthesis. Dynamic control of the

rotational speed would be the next logical step in the development of molecular motors.

Locking the rotation by employing an acid-base responsive self-complexing

pseudorotaxane was the first example that allowed for such dynamic control over the

rotary motion.[68]

More recently, an allosteric approach was reported in which metal

complexation was used to alter the speed of rotation.[69]

Complexation of different metals

to the stator part of a second generation molecular motor caused different degrees of

contraction of the lower half. As a consequence the steric hindrance in the fjord region

decreased, which resulted in a lower barrier for the THI.

18

Chapter 1

Precise control of the speed of rotation in a dynamic fashion remains challenging but the

first examples have shown that lengthy syntheses can be avoided and motor speed can be

altered in situ. Controlling speed by external effectuators (metal/ion binding, pH, redox) or

tuning in response to chemical conversions (catalysis) or environmental (matrix, surface)

constraints offers exciting opportunities for more advanced motor functioning.

1.2.2 Shifting the excitation wavelength

A major challenge in the field of photochemical switches and motors is to move away from

the use of damaging UV light because it limits the practicality in soft materials and

biomedical applications.[70,71]

For this reason, it is important to shift the irradiation

wavelengths towards the visible spectrum.[72]

The most straightforward method is to make

changes to the electronic properties of the motors in such a way that the molecule is able

to absorb visible light. However, such changes may be detrimental to the

photoisomerization process. The first successful example of a visible light-driven

molecular motor made use of a push-pull system to red-shift the excitation wavelength.[73]

This second generation motor comprised a nitro-acceptor and a dimethylamine-donor

substituent in its lower half, which allowed for photoexcitation with 425 nm light. An

alternative strategy, that is often used to red-shift the absorption of molecular

photoswitches, relies on the extension of the system. Indeed upon extension of the

aromatic system of the stator half of second generation motors, unidirectional rotation

could be induced by irradiation at wavelengths up to 490 nm.[74]

Apart from these methods that focus on altering the HOMO-LUMO gap, alternative

strategies based on metal complexes are highly promising. For example, palladium

tetraphenylporphyrin was used as a triplet sensitizer to drive the excitation of a molecular

motor.[75]

Isomerization of the motor was shown to occur by triplet-triplet energy transfer,

upon irradiation of the porphyrin with 530-550 nm light. In a related example, a molecular

motor was incorporated as a ligand in a Ruthenium(II)-bipyridine complex.[76]

Irradiation

with 450 nm into the metal-to-ligand charge transfer band resulted in unidirectional

rotation.

These examples illustrate that there are multiple viable strategies to red-shift the

excitation wavelength of molecular motors. However, the change of the wavelength

region at which these motors can be operated is still modest. Moving further away from

UV light towards red light or even near-infrared remains a major challenge. There are

several strategies that have shown promising results for photoswitches, such as

diarylethenes and azobenzenes, that have not been applied to molecular motors yet.[72]

For example, multiphoton absorption processes using upconverting nanoparticles[77]

or

two-photon fluorophores[78]

should be considered in future studies.

19

Molecular rotary motors: Unidirectional motion around double bonds

1.2.3 Improvement of the photochemical efficiency

Improving the efficiency of the photochemical isomerization process has proven to be

difficult as it not as well understood as the thermal isomerization process. Typically,

quantum yields below 2% are observed for E/Z photoisomerization of second generation

motors.[52,79]

To improve the yield, a detailed understanding of the excited state dynamics

is required. Over the last decade, a combination of advanced spectroscopic studies and

quantum chemical calculations have been used to gain insight in the mechanism of the

photochemical isomerization. Using time-resolved fluorescence and picosecond transient

absorption spectroscopy, a two-step relaxation pathway was observed after the initial

excitation to the Franck-Condon excited state.[50,79,80]

Within 100 femtoseconds, a bright

(i.e. fluorescent) state relaxes to an equilibrium with a lower lying dark (i.e. non-

fluorescent) state. Based on femtosecond stimulated Raman spectroscopy, supported by

quantum chemical calculations, it has been postulated that this process is accompanied by

elongation and weakening of the central double bond.[81–84]

Solvent viscosity studies

showed that this process is independent of solvent friction, which is consistent with a

volume conserving structural change.[79,85]

The dark excited state, formed after this first

relaxation, has a lifetime of approximately 1.6 picosecond and relaxes back to the ground

state to either the stable or unstable form via conical intersections (CIs). Relaxation to the

ground state leaves excess vibrational energy which is dissipated to the solvent at the tens

of picoseconds timescale.[81]

The relative long lifetime of the dark state is attributed to the

fact that a high degree of twisting and pyramidalization of one of the carbons of the

central double bond is required to reach the CI.[84]

Recent studies showed that this

relaxation to the ground state, which is associated with twisting and pyramidalization, is

not dependent on the size of the substituents,[85]

while it is dependent on viscosity. This

observation suggests that the motion that accompanies the relaxation to the ground state

is not necessarily a complete rotation of the halves but rather occurs only at the core of

the molecule.

The ability to control CIs could lead to major improvements, as they play an important role

in the efficiency of the photochemical step. To improve the efficiency of molecular

motors, Filatov and coworkers investigated the factors influencing the CIs in a theoretical

study.[86,87]

The calculations predict that by placing electron withdrawing groups close to

the central axle, such as an iminium, the character of the CI changes from a twist-

pyramidalization to a twist-bond length alteration. This effectively changes the mode of

rotation from a precessional motion for current motors to an axial motion with higher

efficiency. These computational designs have already inspired the development of new

photoswitches with increased efficiency,[88]

but have not yet been applied to motors and

should be taken into account in attempts to increase the efficiency.

20

Chapter 1

1.2.4 Redox-driven motors

As an alternative to the use of (UV-Vis) light to power molecular motors we considered

designing an electromotor taking advantage of redox processes. Preliminary studies

towards using overcrowded alkenes as redox-driven molecular motors are promising.[89]

A

rotary cycle is envisioned, in which consecutive oxidation/reduction cycles would

electrochemically form the unstable state, which then undergoes a THI to afford the stable

state, completing 180° rotation (Scheme 1.2). Unfortunately, the stereogenic center was

found to be susceptible to deprotonation, leading to an irreversible double bond shift in

which the central axis is converted to a single bond. As this type of degradation pathway

impedes any successful directional motion, a different design has to be made.

Quaternization of the stereogenic center by replacing the hydrogen for a fluorine atom

would prevent deprotonation. It was recently shown that such fluorine-substituted

molecular motors with quaternary stereocenters are still capable of unidirectional

rotation when irradiated by light, making them excellent candidates to be studied as

redox-driven molecular motors.[90]

Scheme 1.2. Proposed rotational cycle for a redox-driven molecular motor.

1.3 Alternative motor designs

In 2006, Lehn proposed a new type of light-driven molecular motor derived from

imines.[91]

The design is based on the two types of E/Z-isomerization processes that imines

can undergo, namely a photochemical isomerization and a thermal nitrogen inversion. A

two-step rotational cycle was proposed, starting with a light induced E/Z-isomerization,

which has an out-of-plane rotational mechanism (Scheme 1.3). A thermally activated in-

plane nitrogen inversion involves a planar transition state which would convert the

system back to the original state. These two combined processes would lead to a net

21

Molecular rotary motors: Unidirectional motion around double bonds

rotational motion as both follow a different pathway. Placing a stereogenic center next to

the imine leads to preferential rotation by favoring the direction of the photochemical

isomerization. This is different from the other examples of double bond motors, as

directionality is induced here in the photochemical step, rather than the thermal

isomerization step.

Scheme 1.3. Proposed mechanism for an imine-based molecular motor.

Based on these design principles, Lehn and coworkers reported in 2014 on the synthesis of

the first rotary motor based on imines,[92]

i.e. N-alkyl imine 14 bearing a stereocenter next

to the central imine (Scheme 1.4). Because of the twisted shape of the lower half and E-Z

isomerism of the imine four stereoisomers are formed. A helicity inversion does not occur

under the experimental conditions due to the relatively high barrier for this process

compared to the nitrogen inversion. Under thermodynamic equilibrium, there is a

preference for (S,M)-cis over (S,P)-trans, whereas there is not a major preference for

either (S,P)-cis or (S,M)-trans. Photochemical isomerization occurs upon irradiation with

254 nm light and at PSS the ratio is shifted towards (S,P)-trans relative to (S,M)-cis, while

the ratio of the other two isomers remains unaffected by irradiation. Heating up the

mixture of isomers to 60° C for 15 h allows for the nitrogen inversion to occur, restoring

the original distribution of diastereomers.

22

Chapter 1

Scheme 1.4. A two-step molecular rotary motor based on imines.

Both processes are equilibrium reactions and therefore both forward and backward

reactions can occur. However due to preferred formation of one of the isomers in each

step, overall a net rotation occurs. During their investigations, it was found that annealing

a benzene ring to the lower half is essential for this two-step motor as it effectively

increases the thermodynamic barrier for the helicity inversion. Interestingly, when this

inversion can occur, a molecular motor with a four-step rotary cycle is obtained,

reminiscent of the cycle for motors based on overcrowded alkenes. That is, two

photochemical isomerization steps and two thermally activated ring inversions give rise to

360° rotation. To show that imines can be used as two-step molecular motors in a more

general sense and to provide more experimental and theoretical proof for the rotational

behavior, camphorquinone imines were synthesized in a follow-up study.[93]

One of the major advantages of imine-based molecular motors is that many types of

imines with different properties can be easily synthesized through simple condensation

reactions starting from commercially available materials. Furthermore, fine-tuning of the

speed of these motors can be achieved through controlling the barrier for N-inversion. The

barrier for this process depends largely on the substituent at the N-atom, providing a good

handle to alter the speed of rotation. The assumption that there is a preferred direction

of rotation in the photochemical E/Z-isomerization in chiral imines due to the

unsymmetrical excited state surface is very plausible, but further experimental support to

unequivocally prove their preferred direction of rotation is warranted. These

photoinduced isomerization processes often occur at the picosecond timescale, making it

very difficult to obtain direct evidence. Potentially, quantum mechanical calculations can

aid in exploring the excited state surface.

23

Molecular rotary motors: Unidirectional motion around double bonds

In 2015, Dube and coworkers introduced a light-driven molecular motor based on a

thioindigo unit fused with a stilbene fragment (Scheme 1.5).[94]

The design and rotational

cycle resemble that of the molecular motors based on overcrowded alkenes with the

distinct difference that a sulfoxide stereogenic center is present. Due to the steric

crowding around the central axle, the substituents of the central double bond are twisted

out of plane, giving the molecule a helical shape. The helicity is dictated by the chirality of

the sulfoxide. The behavior of this motor was examined by UV/Vis and 1H-NMR

spectroscopy showing that, in analogy to the overcrowded alkene motors, the rotational

cycle consists of four steps: Two alternating sets of photochemical and thermal

isomerization steps. The photochemical isomerization could be induced by light of

wavelengths up to 500 nm and a frequency of rotation of 1 kHz at room temperature was

determined. During the 1H-NMR studies, only the (E,S,M)-15 unstable state was observed,

whereas the (Z,S,M)-15 state could not be detected, presumably because the THI is too

fast. This hypothesis was supported by detailed DFT calculations showing a four-step

unidirectional rotary cycle. More recently, a more sterically crowded and, therefore,

slower motor was synthesized, which allowed for the direct observation of the fourth

state.[95]

Scheme 1.5. Rotational cycle for hemithioindigo-based motors.

1.4 Outlook

Since the first development of light-driven molecular rotary motors two decades ago,

great progress has been made in controlling unidirectional rotation around double bonds.

24

Chapter 1

In particular, the overcrowded alkene-based molecular rotary motors have been

thoroughly investigated. Various designs are now increasingly applied to control dynamic

functions,[12]

however, for a wider range of applications of these motors, further

improvements are essential. For example, the use of longer irradiation wavelengths as

usually the photochemical isomerization steps are induced by UV light, which is harmful

and thus impedes application in chemical biology and materials science. The first visible-

light-driven motors that can be powered with light up to 500 nm have recently been

introduced, but more powerful strategies such as multiphoton absorption or photon

upconversion need to be explored since they will afford a major red-shift in the irradiation

wavelength, preferably even into the near-IR region. Although the influence of structural

changes on the speed of rotation of these motors has been well established,

supramolecular and metal-based approaches that allow for speed adjustments with

multiple stimuli are highly promising. Increasing the efficiency of molecular motors is a

more complex problem that offers another nice challenge also in view of potential use in

nanoscale energy conversion and storage as well as performance of mechanical work by

future rotary motor-based molecular machines. In this regard, theoretical studies could

aid in improving the efficiency and motor design. Another major challenge for molecular

motors that comprise a stereogenic center is to obtain sufficient quantities of

enantiopure material, which is needed to explore new applications in particular towards

responsive materials. Enantioselective synthetic routes towards first and second

generation motors have been recently developed[29,96,97]

and a chiral resolution method by

crystallization of first generation motors offers important perspectives.[98]

All these fundamental challenges have to be considered in the perspective of molecular

machines; control of functions and the design of responsive materials. Tuning molecular

motors to operate in complex dynamic systems will require among others synchronization

of rotary and translational motion, precise organization and cooperativity, as well as

amplification of motion along length scales. A first approach towards coupled motion was

recently reported by our group, in which the rotary motion of the molecular motor is

transferred to the synchronized movement of a connected biaryl rotor.[99]

The prospects

for controlling motion at the nanoscale and beyond will continue to provide fascinating

challenges for the molecular designer and many bright roads for the molecular motorist in

the future.

1.5 Outline of this thesis

As outlined in the previous sections, for molecular motors to reach their full potential,

challenges have to addressed. In this thesis, some of these challenges are addressed such

as visible light addressability (Chapters 2 and 3) and dynamic control of rotary motion

(Chapter 4). Additionally, making use of the intrinsic chirality of molecular motors, they

25

Molecular rotary motors: Unidirectional motion around double bonds

are incorporated in supramolecular coordination complexes and polymers as chiroptical

multi-state switches.

Chapter 2 describes the synthesis and characterization of a second generation molecular

motor based on pyrene. By extending the aromatic core of the motor, the excitation

wavelength is red-shifted to the visible light region. Even though pyrene is well-known for

its fluorescent behavior, the molecular motor retains its function without significant

fluorescence.

The aim of Chapter 3 is red-shifting the excitation wavelength of molecular motors as well,

but by developing a new type of molecular motor based on oxindole. Their four step

rotation cycle is first explored using DFT. The motors are easily synthesized in one step

using a Knoevenagel condensation. NMR and UV/vis studies show that these motors can

be driven by visible light of wavelengths up to 505 nm.

Chapter 4 addresses the dynamic control of rotary motion in a multiphotochromic hybrid.

A molecular motor is coupled with a dithienylethene switch, which allows gating of the

rotary function. Photochemical ring closing of the dithienylethene switch moiety results in

inhibition of the rotary motion.

In Chapter 5, molecular motors are used as photochromic ligands in a supramolecular

coordination complex. A Pd2L4 complex is formed employing a first generation molecular

motor bearing pyridine moieties. X-Ray and CD studies supported by DFT calculations

show that only homochiral cages are formed. Photochemical switching between different

states of the molecular motor is possible, changing the morphology of the cage.

Additionally, tosylate anions were shown to bind to in cavity of the cages.

Finally, Chapter 6 describes the incorporation of molecular motors in polymers. First

generation molecular motors are copolymerized with fluorene moieties using a Suzuki

polymerization, with the goal to control the conformation of the polymer using light.

Unfortunately, photoswitching in the polymer appears to be inhibited to a large extent

and instead fluorescence is observed.

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